August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.

May 30, 2013 (NOT-OD-13-074) -
NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.

This Funding Opportunity Announcement (FOA) issued by the
National Institute of Allergy and Infectious Diseases (NIAID) invites
applications for implementation of investigator-initiated, non-high-risk
clinical trials. The trials must be hypothesis-driven, related to the
research mission of the NIAID and considered a high priority by the
Institute. Investigators are encouraged to visit the NIAID website for
additional information about the research mission and high-priority research
areas of the NIAID (http://www3.niaid.nih.gov/about/whoWeAre/planningPriorities/).
Only one clinical trial may be proposed in each NIAID Clinical Trial
Implementation (R01) Grant application.

Key Dates

Posted Date

March 22, 2013

Open Date (Earliest Submission Date)

May 4, 2013

Letter of Intent Due Date(s)

30 days before the application due date

Application Due Date(s)

June 4, 2013; September 11, 2013; January 13, 2014; May
13, 2014; September 11, 2014; January 13, 2015; May 13, 2015; September 11,
2015; and January 13, 2016, by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

AIDS Application Due Date(s)

June 4, 2013; September 11, 2013; January 13, 2014; May
13, 2014; September 11, 2014; January 13, 2015; May 13, 2015; September 11,
2015; and January 13, 2016, by 5:00 PM local time of applicant organization.

Scientific Merit Review

September 2013; January 2014; May 2014; September 2014;
January 2015; May 2015; September 2015; January 2016; and May 2016

Advisory Council Review

October, 2013, January 2014; May 2014; October 2014;
January 2015; May 2015; October 2015; January 2016; May 2016

Earliest Start Date

March 2014; August 2014; December 2014; March 2015; July
2015; December 2015; March 2016; July 2016; December 2016

Expiration Date

January 14, 2016

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH
Guide for Grants and Contracts). Conformance to all requirements (both
in the Application Guide and the FOA) is required and strictly enforced. Applicants
must read and follow all application instructions in the Application Guide as
well as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

There are several options to submit your application to the agency through Grants.gov. You can use the ASSIST system to prepare, submit and track your application online. You can download an application package from Grants.gov, complete the forms offline, submit the completed forms to Grants.gov and track your application in eRA Commons. Or, you can use other institutional system-to-system solutions to prepare and submit your application to Grants.gov and track your application in eRA Commons. Learn more.

This Funding Opportunity Announcement (FOA) issued by the
National Institute of Allergy and Infectious Diseases (NIAID) invites
applications for implementation of investigator-initiated, non-high-risk
clinical trials.

A clinical trial is defined by NIH as:

“A prospective biomedical or behavioral research study of
human subjects that is designed to answer specific questions about biomedical
or behavioral interventions (drugs, treatments, devices, or new ways of using
known drugs, treatments, or devices). Clinical trials are used to determine
whether new biomedical or behavioral interventions are safe, efficacious, and
effective”.

The proposed trial must be hypothesis-driven, related to the
research mission of the NIAID and address a research area considered a high
priority by the Institute. For AIDS-related clinical trials, the Institute
encourages investigator-initiated studies that include but are not limited to
biobehavioral trials and equally as important, trials and studies that also
explore disease pathogenesis.

This FOA will utilize the NIAID Clinical Trial
Implementation (R01) Grants, which support implementation of
investigator-initiated, non-high-risk clinical trials, and will run in parallel
with two related FOAs, PAR-13-151 and PAR-13-150,
that invite applications for NIAID Clinical Trial Planning (R34) Grants, which
support planning activities for investigator-initiated clinical trials, and the
NIAID Clinical Trial Cooperative Agreement (U01) award mechanism, which support
implementation of high-risk clinical trials, respectively.

Background

Over the past three years, NIAID committed over $2 billion to
clinical research, of which $1.5 billion was devoted to clinical trials.
Clinical trials are one research strategy NIAID uses to improve the
understanding of the clinical mechanisms of infectious, immunologic, and allergic
diseases or to improve prevention, diagnosis, and treatment. For additional
information about the mission, strategic plan, and research interests of the
NIAID, applicants are encouraged to consult the NIAID web site http://www3.niaid.nih.gov/about/whoWeAre/planningPriorities/.

Although clinical research infrastructure is crucial to
furthering the Institute’s research, NIAID recognizes that additional models of
clinical research may be important to advancing its research mission;
therefore, NIAID has established the investigator-initiated clinical trial
program for clinical trials that cannot or will not be conducted through
existing NIAID-supported clinical trial infrastructure. This program consists
of support for the NIAID Clinical Trial Planning (R34) Grant, the NIAID
Clinical Trial Implementation (R01) Grant and the NIAID Clinical Trial Implementation
(U01) Cooperative Agreement. The NIAID Clinical Trial Implementation (R01)
Grant (PAR-13-149)
FOA is designed to support non-high-risk clinical trials, while the NIAID Clinical
Trial Implementation (U01) Cooperative Agreement (PAR-13-151)
FOA is designed to support high-risk clinical trials, as defined by NIAID below
and in the associated policy statement (see NOT-AI-10-024).
The NIAID Clinical Trial Planning Grant (R34) is available to support planning
activities associated with either high- or non-high-risk clinical trials.
However, the NIAID Clinical Trial Planning (R34) Grant (PAR-13-150)
FOA is not a prerequisite for either NIAID implementation award. If a clinical
trial is ready for implementation, and readiness is adequately supported by
appropriate documentation, the R01 or U01 application may be submitted to the
appropriate FOA.

The NIAID Clinical Trial Implementation (R01) Grant supports
implementation of non-high-risk clinical trials that address research areas
that are well matched with the mission and goals of NIAID.

A high-risk clinical trial is defined by the NIAID as having
one or more of the following attributes:

provision of a non-routine intervention, that is, an intervention
or non-routine use of an intervention that would not otherwise be provided for
the condition under study in the local facility where the study is being
conducted;

administration of an unlicensed product; or

administration of a licensed product for an unapproved
indication.

A non-high-risk trial would not have any of the attributes
listed above; for example, it would involve provision of a routine intervention
and administration of a licensed product for an approved indication. Applicants
are strongly encouraged to contact NIAID staff listed in Section VII. Agency Contacts for questions
concerning the classification of the proposed clinical trial.

For the purposes of this FOA, implementation support is
defined as support for activities related to the conduct of the clinical trial,
including, but not limited to:

training of study personnel;

enrollment and recruitment of study subjects;

data collection, management and quality control;

laboratory work and data analyses;

study management and oversight;

establishment of committees to manage the complexity of the
trial; and

preparation of the final study report; and other related
post-enrollment activities.

Each NIAID Clinical Trial Implementation (R01) award will
support the implementation of a single clinical trial; applications that
include more than one clinical trial will not be reviewed. An overview of the
state of the science, current status and relevance of the trial, and discussion
of the clinical protocol must be presented in the application. Applicants must
propose a time-sensitive, milestone-driven clinical trial and describe the
clinical trial stages, criteria for completion of the stages and contingency
plans for each stage. Any anticipated impediments that could require a revision
in the timeline must be identified and accompanied by a discussion of
alternative approaches. The trial must be hypothesis-driven, and have clear
primary and secondary endpoints. A description of the study population, why it
is an appropriate group to study the research question(s) posed, subject
eligibility, inclusion and exclusion criteria, and a feasible recruitment and
enrollment plan must also be included. Statistical methods appropriate for the
study design, and adequate plans for data monitoring and safety are required.
All clinical trial planning activities must be completed by the time of
application submission and investigators must be ready to implement the
proposed trial at the time of award.

NIAID reserves the right to specify: 1) whether an IND (Investigational
New Drug)/IDE (Investigational Device Exemption) application should be
submitted to an appropriate regulatory agency; 2) the entity (NIAID, primary
awardee, etc.) who will hold the IND/IDE; and 3) the requirements for the
establishment of a DSMB(Data Safety Monitoring Board)/SMC (Safety Monitoring
Committee).

Investigators are referred to NIAID’s Clinical Research
Toolkit website (http://www.niaid.nih.gov/labsandresources/resources/toolkit/pages/default.aspx ) for protocol templates and guidance, clinical research resources, and links
to program divisions. Investigators are strongly encouraged to contact NIAID’s
program divisions (Agency Contacts) for information regarding division-specific
clinical research policies and procedures.

Milestones

Delineation of milestones is a key characteristic of the
NIAID Clinical Trial Implementation (R01) Grant. A milestone is defined as a
scheduled event in the project timeline, signifying the completion of a major
project stage or activity.

Applications must include a series of milestones for
completion of the clinical trial and provide contingency plans should there be
delays in attaining them. The milestones will undergo peer review and will be
incorporated into the terms of award.

Applications that propose to conduct planning activities are
not responsive to this FOA and will not be reviewed. Investigators seeking
support for the planning and design of clinical trials should refer to the
NIAID Clinical Trial Planning (R34) Grant FOA (PAR-13-150).

NIAID R01 clinical trial research project grants will NOT
provide support for clinical trials that fall outside the mission and high-priority
research areas of the NIAID and will not support more than one clinical trial
in a single application.

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or
both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

New
Resubmission
Revision

The OER
Glossary and the SF424 (R&R) Application Guide provide details on
these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations
and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets are not limited, but need to reflect
actual needs of the proposed project.

Award Project Period

The scope of the proposed project should determine the
project period. The maximum period is 5 years.

NIH grants policies as
described in the NIH
Grants Policy Statement will apply
to the applications submitted and awards made in response to this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH
Policy on Late Submission of Grant Applications states that failure to
complete registrations in advance of a due date is not a valid reason for a
late submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number and SAM registration in order to complete the
eRA Commons registration. Organizations can register with the eRA Commons as
they are working through their SAM or Grants.gov registration. eRA Commons
requires organizations to identify at least one Signing Official (SO) and at
least one Program Director/Principal Investigator (PD/PI) account in order to
submit an application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should
work with their organizational officials to either create a new account or to
affiliate an existing account with the applicant organization’s eRA Commons
account. If the PD/PI is also the organizational Signing Official, they must
have two distinct eRA Commons accounts, one for each role. Obtaining an eRA
Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the
same as one already reviewed within the past thirty-seven months (as described
in the NIH
Grants Policy Statement), except for submission:

To an RFA of an application that was submitted previously as an
investigator-initiated application but not paid;

Of an investigator-initiated application that was originally
submitted to an RFA but not paid; or

Of an application with a changed grant activity code.

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

Required and Optional Components

The forms package associated with this FOA includes all
applicable components, required and optional. Please note that some
components marked optional in the application package are required for
submission of applications for this FOA. Follow all instructions in the SF424
(R&R) Application Guide to ensure you complete all appropriate “optional”
components.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Other
Attachments: Provide the following information:

1. Clinical Protocol Synopsis

The filename "Clinical Protocol Synopsis.pdf"
should be used and will be reflected in the final image bookmarking for easy
access for reviewers.

The clinical protocol synopsis must include the following
information:

A description of the study population, including subject
eligibility and inclusion/exclusion criteria;

Sampling, recruitment and enrollment plans, including a
discussion of the availability of subjects for the proposed study and the
ability of enrollment center(s) to recruit and retain the proposed number of
subjects;

The process to be used for obtaining informed consent and, if
applicable, assent;

Approaches to be used for retention, cooperation and follow-up of
subjects and to address any anticipated changes in the composition of the study
population over the course of the trial;

Methods of assignment of subjects to study groups and of
randomization;

If appropriate to the study, a description and justification for
the selection of the dose, frequency and administration of the intervention(s);

A description of each enrollment site and how data from the
site(s) will be obtained, managed, and protected;

Descriptions of all clinical, laboratory, physiological, and/or
behavioral tests to enable the research questions to be answered; and

A description of the data management and quality control plan,
including methods for monitoring the quality and consistency of the
intervention(s) and data collection; policies and methods for ensuring blinding
of study results; and data confidentiality and subject privacy.

Applications that lack the Clinical Protocol Synopsis are
nonresponsive and will not be peer reviewed.

2. Statistical Analysis Plan

The filename "Statistical Analysis Plan.pdf"
should be used and will be reflected in the final image bookmarking for easy
access for reviewers.

This plan is critical to knowing whether applicants have
selected the correct cohort size based on proper power calculations and/or are
using the most appropriate methods to analyze the resulting data and make
correct conclusions at the end of the study. The ability to make conclusions of
primary outcomes other than safety will be particularly important in small
studies.

Applications that lack the Statistical Analysis Plan are
nonresponsive and will not be peer reviewed.

3. Data and Safety Monitoring (DSM) Plan

The filename "Data and Safety Monitoring Plan.pdf"
should be used and will be reflected in the final image bookmarking for easy
access for reviewers.

The DSM plan should be commensurate with the risk level of
the proposed clinical research ND must be included for all clinical trials (see http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
All applications or study protocols must include a general description of the
monitoring plan, policies, procedures, responsible entities, and approaches to
identifying, managing and reporting reportable events (adverse events and
unanticipated problems), to the applicable regulatory agencies (e.g.,
Institutional Review Board (IRB)), the Office of Biotechnology Activities (as
appropriate), the Office of Human Research Protections, the Food and Drug
Administration, and the Data and Safety Monitoring Board (if one is used).

The DSM Plan must address the following areas:

Who will manage and conduct the monitoring;

What will be monitored;

Proposed monitoring time points;

Where the monitoring will occur;

How the reportable events will be managed and reported; and

How sites/centers, and participating facilities (labs,
pharmacies) will be monitored.

Applications that lack the DSM Plan are nonresponsive and
will not be peer reviewed.

4. Milestone Plan and Complete Clinical Protocol

The filename “Milestone Plan and Complete Clinical Protocol.pdf"
should be used and will be reflected in the final image bookmarking for easy
access for reviewers.

Applicants are required to provide detailed project
performance and timeline objectives in a section entitled “Milestone Plan”.
This section must include:

A timeline for the following general milestones, as applicable;

Completion of regulatory approvals;

Enrollment of the first subject;

Enrollment of 25%, 50%, 75% and 100% of the projected recruitment
time period for all study subjects, including women, minorities and children
(as appropriate);

Applications that lack the Milestone Plan and/or the
Complete Clinical Protocol are nonresponsive and will not be reviewed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide
must be followed.

R&R Budget

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

This FOA uses non-modular budget formats described in the SF
424 Application Guide.

Because all applications must include detailed scientific
and operational plans, funding needs for the entire trial and data analysis
period must also be included. Investigators must submit a complete, justified,
individual budget for each year of support requested. All costs requested and
all changes in budgets after the first year should be clearly identified and
justified. Separate itemized budgets must be prepared for each subcontract
and/or for each collaborating site, if multiple sites or cores are proposed. If
parts of the costs of the trial are to be borne by sources other than NIH,
these contributions must be presented in detail along with supporting letters
signed by individuals who have the authority to make fiduciary commitments on
behalf of the institution (see Letters of Support in the PHS 398 Research Plan below).
These outsource costs do not constitute cost sharing as defined in the current
NIH Grants Policy Statement and should not be presented either as part of the
requested budget or as Estimated Project Funding.

Further information concerning budget preparation may be
obtained from the Financial/Grants Management Contact(s) listed in Section
VII. Agency Contacts.

PHS 398 Cover Letter

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

A letter that summarizes the discussion during prior
consultation with NIAID may be obtained from the appropriate NIAID Division
Director and attached as a .pdf file to the PHS398 Cover Letter file.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Specific
Aims: The goals of the trial and the expected outcome(s) should
be concisely stated in the Specific Aims section. The specific objectives of
the trial must be clearly and concisely presented, including a specification of
the primary and major secondary endpoints to be measured. There should be a
clear explanation of the importance of various endpoints.

Research
Strategy: The following three sections comprise the Research
Strategy: Significance, Innovation, and Approach.

The Research Strategy
must include:

a discussion of the significance of the problem being studied,
the need for the trial, and the potential impact of the results of the trial,
as well as how the trial will test the hypothesis(es) proposed;

a concise description of the overall strategy, methodology and
analyses to be used to accomplish the goals and specific aims of the trial;

a description of and rationale for the proposed study design;

a description of the intervention to be tested and the protocol
to be followed in each arm of the trial, including a discussion of potential
biases or challenges in the protocol and how they will be addressed;

statistical methods that are appropriate for the study design,
including sample size and power calculations and the underlying assumptions
(and data) used to link these calculations to the endpoints and to the
hypothesis(es) being tested;

a discussion of studies that led to the proposed clinical trial
and information or data from preliminary studies which address the need for and
the feasibility of the trial; and

a description of the study organization and administration,
including, but not limited to: a description of committee structures needed to
manage the complexity of the trial; the role of any internal or external
advisory committees; the oversight, responsibilities, and coordination of any
sites or cores proposed; and the role of any sub-contractors or service
providers for personnel or facilities.

A description of the plans to implement and monitor Good Clinical
Practices (GCP), Good Laboratory Practices (GLP) and Good Manufacturing
Practices (GMP), as appropriate.

Letters
of Support: In the Letters of Support section of the Research
Plan, provide all appropriate letters of support, including any letters
necessary to demonstrate the support of consortium/site participants, cores,
laboratories, pharmacies and other collaborators. If co-funding or in-kind
support is planned from non-NIH sources, letter(s) outlining details of the
commitment (e.g. type, amount and source of support), signed by a business
official on organization letterhead, must be included in the Letters of Support
section.

Resource
Sharing Plan: Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424
(R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs
requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

The following additional documents must be included in the
Appendix material in the order listed below. Place all documents in a single
.pdf file:

the informed consent form(s) and, if applicable, assent form(s)

identification and qualifications of clinical trial site(s),
pharmacies and laboratories

copies of data collection forms, questionnaires or other relevant
materials

the Investigator’s Brochure or equivalent for the study
products(s)

the Table of Contents of the Manual of Operations

a comprehensive Laboratory Plan

documentation of availability of study agents as well as plans
and support for acquisition and administration of study agent(s)

documentation of cofounding of clinical trials from partners, as
appropriate

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies
described in the NIH
Grants Policy Statement, and procedures for foreign institutions described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications
before the due date to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the
status of the application in the eRA Commons, NIH’s electronic system for grants
administration. NIH and Grants.gov systems check the application against many
of the application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the application
due date. If a Changed/Corrected application is submitted after the deadline,
the application will be considered late.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the System for Award Management. Additional information may be
found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review and responsiveness by
components of participating organizations, NIH. Applications that are
incomplete and/or nonresponsive will not be reviewed.

Responsiveness
Criteria

Responsive applications include: an appropriate Clinical
Protocol Synopsis, Statistical Analysis Plan, Data Safety and Monitoring Plan,
Milestone Plan and Complete Clinical Protocol, Informed consent, and if
applicable, assent forms, Comprehensive laboratory plan and Table of Contents
for the Manual of Operations. Applications that omit any of these components
will be considered non-responsive and will not be reviewed.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in
any year (excluding consortium F&A) must contact NIH program staff at least 10 weeks before
submitting the application and follow the Policy on the Acceptance for Review
of Unsolicited Applications that Request $500,000 or More in Direct Costs as
described in the SF424 (R&R) Application Guide.

Prior
Consultation with NIAID

Consultation with NIAID staff at least 10 weeks prior to the
application due date is strongly encouraged for submission of the NIAID
Clinical Trial Implementation (U01) Cooperative Agreement application,
including new and resubmission applications. If requested, NIAID staff will
consider whether the proposed clinical trial meets the goals and mission of the
Institute, whether it addresses one or more high priority research areas, and
whether it is appropriate to conduct as an investigator-initiated clinical
trial. NIAID staff will not evaluate the technical and scientific merit of the
proposed trial; technical and scientific merit will be determined during peer
review using the review criteria indicated in this FOA. NIAID staff members are
also available to work with potential applicants to determine the risk level of
the proposed trial and delineate all documentation that will be needed at the
time of application submission. During the consultation phase, if the proposed
trial does not meet NIAID’s programmatic needs or is not appropriate as an
investigator-initiated clinical trial, applicants will be strongly encouraged
to consider other Funding Opportunities. NIAID reserves the right to provide
support for clinical trials through other available mechanisms supported by
NIAID. If NIAID ascertains that substantial additional planning may be
necessary, or that substantial staff involvement may not be necessary, the
applicant will be encouraged to consider funding applying for under the
Clinical Trial Planning Grant (R34) (PAR-13-150)
or the Clinical Trial Implementation Cooperative Agreement (U01) FOA (PAR-13-151),
respectively.

A letter that summarizes the discussion during prior
consultation may be obtained from the appropriate NIAID Division Director and
attached as a .pdf file to the PHS398 Cover Letter file.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-13-030.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field? If proposed, do the mechanistic studies
contribute to the understanding of the disease or treatment? Are the study
objectives(s) and hypothesis(es) adequately defined?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD/PI, do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project? Do the
PD/PIs and key personnel have the expertise and ability to organize, manage and
implement the proposed clinical trial and meet milestones and timelines? Do
they have appropriate expertise in study coordination, data management and
statistics? For multicenter trials, is the organizational structure appropriate
and does the application identify a core of potential center investigators and
staffing for a coordinating center?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed? If applicable, does
the proposed multi-disciplinary trial leverage accelerated vaccine, adjuvant,
therapeutic, immunotherapeutic, or diagnostics product development,
innovatively?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be
managed? Does the application adequately address the following: the
intervention, study agent(s), mode of delivery; ancillary therapies and plans
for acquisition and handling of study agent(s)? Does the application adequately
address all aspects of proposed clinical trial, e.g., the study population,
inclusion/exclusion criteria, plans for recruitment outreach, enrollment,
retention, informed consent or assent form, differences in the intervention
effect due to sex/gender and race/ethnicity as applicable and primary and
secondary endpoints? Are potential ethical issues adequately addressed? Are
proposed mechanistic studies feasible and would they contribute to the understanding
of the disease or treatment? Does the application adequately address the
statistical hypothesis and analysis including sample size and power
calculation? Are the proposed milestones and timelines appropriate? Does the
application adequately address Good Clinical Practices (GCP), Good Laboratory
Practices (GLP), and Good Manufacturing Practices (GMP) compliance? For
multi-center trials, does the application adequately address
standardization/quality control of, and adherence to, the clinical protocol and
data collection or distribution guidelines?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements? Does the application adequately address plans to add or drop
enrollment centers, as needed? Is there an available pool of the eligible
volunteers as trial participants? If international site(s) is/are proposed,
does the application adequately address the complexity of executing the
clinical trial?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and
Children

When the proposed project involves clinical research,
the committee will evaluate the proposed plans for inclusion of minorities and
members of both genders, as well as the inclusion of children. For additional
information on review of the Inclusion section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and injury
to that which is unavoidable in the conduct of scientifically sound research
including the use of analgesic, anesthetic, and tranquilizing drugs and/or
comfortable restraining devices; and 5) methods of euthanasia and reason for
selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the
application as now presented, taking into consideration the responses to
comments from the previous scientific review group and changes made to the
project.

Renewals

Not Applicable

Revisions

For Revisions, the committee will consider the
appropriateness of the proposed expansion of the scope of the project. If the
Revision application relates to a specific line of investigation presented in
the original application that was not recommended for approval by the
committee, then the committee will consider whether the responses to comments
from the previous scientific review group are adequate and whether substantial
changes are clearly evident.

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Applications from Foreign
Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by the National
Institute of Allergy and Infectious Diseases in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Applications will be assigned on the basis of established
PHS referral guidelines to the appropriate NIH Institute or Center. Applications
will compete for available funds with all other recommended applications submitted
in response to this FOA. Following initial peer review, recommended applications
will receive a second level of review by the National Advisory Allergy and
Infectious Diseases Council. The following will be considered in making funding
decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement. Additional information that may be required as
part of “just-in-time” procedures includes: Training materials and plans for
study staff;

Complete Manual of Operations; IRB or Ethical Committee
approval of the final protocol and the informed consent form (and assent form
if applicable); and other necessary approvals (e.g., Institutional biosafety
committee) of the final protocol, as applicable.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

When multiple years are involved, awardees will be required
to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR)
and financial statements as required in the NIH
Grants Policy Statement.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH
Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and
405 of the Public Health Service Act as amended (42 USC 241 and 284) and under
Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.